A WT1 gene (Wilms tumor gene) is a zinc finger transcription factor isolated as a responsible gene for Wilms tumor. Abnormally high expression of the WT1 gene was then confirmed in acute myeloid leukemia and also in various solid cancers (Non Patent Documents 1 to 3), and application of a WT1 protein as a peptide vaccine has been tried.
In recent years, it has been revealed that the WT1 protein has a structure including a repression domain, an activation domain, and a zinc finger domain, which is a DNA-binding domain, and regulates gene expression by binding to an early growth response protein 1 (EGR-1) region. A function as a tumor suppressor gene has also been reported (Non Patent Documents 4 and 5).
In addition, the presence of autoantibodies to the WT1 protein has been revealed. It has been reported that the titer of autoantibody against the WT1 protein is particularly high in blood of hematological cancer or lung cancer (small cell cancer) patients (Non Patent Documents 6 to 8). Higher expression of WT1 mRNA tends to cause poor prognosis. In contrast, it has been reported that a higher blood level of an anti-WT1 antibody tends to cause good prognosis (Non Patent Document 7). Accordingly, it is believed that accurate measurement of the anti-WT1 antibody in patient blood is useful for selection of a method of treatment or monitoring of treatment progress. For example, measurement of an anti-WT1 antibody using a WT1 protein containing the repression domain and the activation domain but lacking the zinc finger as an antigen has been reported (Patent Documents 1 and 2).
However, the mechanism by which an in vivo protein becomes to be recognized as a foreign substance and induces production of an autoantibody thereto is still unclear. In addition, the concentration of the antibody is very low, and a method for detecting an autoantibody with high sensitivity has not been established. Also regarding the anti-WT1 antibody, there is a problem that the known method using a WT1 protein antigen cannot necessarily accurately evaluate the antibody because of the narrow titer distribution of the detected antibody.